The NCI anticipates holding a pre-application conference
call to which all interested prospective applicants are invited. NCI Program
and Review staff persons will explain the goals and objectives of the Barrett’s Esophagus Translational Research Network (BETRNet)
funding opportunity announcements (FOAs), discuss the application peer review
process, and answer questions. Information about this pre-application conference
call will be available at (https://dcb.nci.nih.gov/News/Pages/Barrett'sEsophagusRFA.aspx).

Additional
Overview Content

Executive Summary

Purpose.This National Cancer Institute funding opportunity
announcement (FOA) solicits applications for the Coordinating Center for the Barrett’s Esophagus Translational Research Network (BETRNet). The BETRNet overall objective is to achieve a better
understanding of esophageal
adenocarcinoma (EA) biology, improve EA cancer risk stratification and
prediction, provide strategies for EA prevention, and better define individuals
at risk. BETRNet will include three to four multi-institutional Translational Research Centers (to be supported under a parallel FOA) and a single Coordinating Center (to be supported under this FOA). The BETRNet Research Centers are
designed to conduct innovative high impact transdiciplinary research
focused on ultimate development of validated diagnostic tools as well as
improved patient management. The role of the Coordinating Center will be to support the
overall BETRNet goals and Research Centers in four major areas: Network
coordination; data management and bioinformatics; patient registry with virtual
biorepository; and Network evaluation. Through these
collaborative efforts, BETRNet can accelerate the integration and transformation
of important research findings generated from individual laboratory-based,
clinical, or population studies into clinical applications.

Mechanism of Support. This FOA will utilize
the NIH Cooperative Agreement (U01) funding
mechanism. This FOA is parallel to a separate FOA (RFA-CA-10-014)
utilizing a U54 funding mechanism to support BETRNet Research Centers.

Funds Available and Anticipated Number
of Awards.For this BETRNet Coordinating Center FOA,
the NCI has committed approximately $500,000 in total costs for FY2011 and
$2.5M in total costs over a 5-year period. One Coordinating Center application will be funded.

Budget and Project Period.It is anticipated that the award will not exceed $500,000
per year in total costs. The total project period for an application submitted in
response to this funding opportunity may not exceed 5 years.

Application Research Strategy Length.The U01 Research Strategy section may
not exceed: 12 pages for Overview of the Proposed Coordinating Center; 12 pages for Leadership and Administrative Core; 6 pages for Data
and Bioinformatics Core; 6 pages for Patient Registry/Virtual Biorepository Core; and 6 pages
for Integration and Self-Evaluation Core. See Table of Page
Limits.,
including tables, graphs, figures, diagrams, and charts. Eligible
Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.

Eligible Project Directors/Principal
Investigators (PDs/PIs). Individuals with the
skills, knowledge, and resources
necessary to carry out the proposed research are invited to work with their institution/organization to
develop an application for support. Individuals from underrepresented
racial and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support. NOTE: Investigators
designated as PDs/PIs on any BETRNet Research Center (U54) application
cannot serve as PDs/PIs on the Coordinating Center U01 application.

Number of PDs/c. More than
one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.

Number of Applications. An applicant
institution may submit only one application in response to this FOA.

Resubmissions. Resubmission
applications are not permitted in response to this FOA.

Renewals.Renewal applications
are not permitted in response to this FOA.

This National Cancer Institute (NCI) Funding
Opportunity Announcement (FOA) solicits applications for the BETRNet Coordinating Center, a component of the Barrett’s Esophagus Translational
Research Network (BETRNet).

The
BETRNet overall objective is to achieve a better understanding of esophageal
adenocarcinoma (EA) biology, improve EA cancer risk stratification and
prediction, provide strategies for EA prevention, and better define individuals
at risk. BETRNet will comprise the following components:

Three
to four multi-institutional Translational Research Centers (to
be supported under a parallel FOA RFA-CA-10-014);
and

A
single Coordinating Center (to be supported under this FOA).

The ultimate goal of BETRNet is to decrease the
incidence, morbidity and mortality of EA by addressing opportunities associated
with understanding it’s only accepted precursor lesion, Barrett’s
Esophagus (BE). Research Centers are
expected to explore these opportunities through innovative high
impact transdiciplinary research focused on development of validated risk
assessment tools as well as improved EA patient management. The program is designed
to foster transdisciplinary collaboration within each Research Center and across the Centers. Through these collaborative efforts, BETRNet can accelerate the integration and translation of
important research findings generated from individual laboratory-based,
clinical and/or population studies into clinical applications.

Role
of BETRNet Coordinating Center. The main goal of the BETRNet Coordinating Center is to integrate and aid efforts across
the BETRNet with the objective of facilitating transdisciplinary research. In particular, the BETRNet Coordinating Center will support BETRNet communications
and operations, data management and bioinformatics, patient registry with virtual
biorepository, and Network evaluation.

Background

While the overall
incidence and mortality rate of cancers have declined in recent years, the
incidence of EA has continued to rise. EA now accounts for at least 2% of US
cancer-related deaths in men and has the fastest growing incidence of all
cancers in the United States (U.S.). In the past three decades, EA incidence
has increased more than 600% in men aged 65 years and older and notwithstanding
progress in multimodality therapies, the overall 5-year survival rate is still
estimated at 15%. Furthermore, esophagectomy with or without neoadjuvant
radiation therapy often incurs early postoperative complications and long term
devastating functional abnormalities. Likewise, medical therapies are still
highly toxic, and remain unsatisfactory in response duration and overall
survival benefit. The completion of any therapy for EA is most often followed
by tumor recurrence or distant metastasis that leads to severe morbidities and
eventual death. The natural course of the disease is insidious and
debilitating, becoming clinically apparent only in advanced stages that are
refractory to treatment and are resource-intensive. Effective cancer preventive
measures will benefit not only affected individuals but also the public at
large.

Significance of
Barrett’s Esophagus. Central to the development of cancer
preventative and clinical management measures is the better understanding of
the etiology of EA. Neoplastic progression in the esophagus is a multi-decade
process characterized by genomic instability and accumulation of molecular
alterations in cell clones. Histologically, EA is thought to arise from the
injury of the esophageal mucosa by frequent reflux of gastric contents that
result in a sequence of metaplasia to low-grade dysplasia, high-grade
dysplasia, and carcinoma. The metaplasia to dysplasia phase of this sequence is
known as Barrett’s esophagus. BE is diagnosed in approximately 10% of
patients who are referred to endoscopy for gastroesophageal reflux disease
(GERD) symptoms. BE, the only widely accepted precursor lesion to EA, is
defined as the replacement of the normal squamous epithelium of the distal
esophagus by columnar epithelium with intestinal metaplasia. Patients with BE
are at least 30 times more likely to develop EA than patients without BE.

Inadequate Clinical
Management of At Risk Patients. Currently, chronic GERD patients are
screened for BE and, if diagnosed to have BE, they are subjected to endoscopic surveillance.
Studies demonstrate that patients with malignancy detected at surveillance
endoscopy have cancers at an earlier stage and better survival than those with
no surveillance. The value of surveillance, however, is questioned by other
studies demonstrating that only about 60% of patients diagnosed with EA have a
prior diagnosis of GERD and less than 5% have a prior diagnosis of BE.
Furthermore, although the increased risk of EA in BE patients has been observed
consistently, only 0.5% of endoscopically monitored BE patients progress to EA
per year (with the high-grade dysplasia patients progressing at an annual rate
of 5% to 20%). These findings suggest that despite decades of research, current
management of EA neoplasia is still inadequate because at risk patients are
rarely identified. Moreover, criteria for screening and endoscopic surveillance
still need to be established in a proper randomized trial. Given the threat of
a highly lethal cancer, both patients and physicians typically opt for the most
aggressive strategies for treatment and surveillance even with
procedure-related risks. This situation has perpetuated the extremely low yield
in defining at risk patients by current strategies despite their very high costs.
Clearly, better understanding of the biology of EA carcinogenesis, including
host and environmental factors is urgently needed for effective, individualized
cancer risk evaluation and for improved patient care.

BE as a Model to
Study the Biology of EA. As a model to study the malignant
transformation process, BE offers the potential for rapid scientific and
clinical advances that could be applied to other cancers besides EA. Unlike
most premalignant lesions (e.g., colon adenomas) that are excised after
detection, BE lesions are left in place. Their changes over time can be
monitored endoscopically with relative ease and safety. BE’s long
asymptomatic premalignant phase allows sequential collection of tissues and
other specimens that can be used to study the genetics and molecular biology of
cancer formation as well as the changes caused by environmental exposures,
response to interventions, and the impact of risk and protective factors. From
a biological perspective, molecular alterations associated with Barrett’s
metaplasia such as COX-2 over-expression, inactivation of p53, aneuploidy, and
DNA methylation are common to many solid tumors and can be used as biomarkers
of cancer risk and neoplastic progression. Moreover, these aberrations may be
exploited as potential targets for preventative and therapeutic strategies.

Understanding the
mechanisms that promote the progression of BE to EA and the changes associated
with this precursor lesion, especially at the genomic and proteomic levels,
could eventually lead to novel interventions to prevent malignancy and/or
control the progression of intervention-resistant clones.

Need for
Collaborative Approaches to BE-EA Research. Whereas research on BE-EA
biology has revealed various molecular and cellular alterations associated with
the malignant transformation of BE to EA, systematic studies are needed to assess
the significance of these aberrations for the EA transition. Such
investigations require access to sufficient number of relevant biospecimens and
associated clinical data. This factor limits the capabilities of individual BE
investigators, especially those involved mainly in basic research. Conversely,
interdisciplinary collaborations among basic, translational, and clinical investigators
and sharing resources (including biospecimens) across institutions offer the
potential to advance BE-EA research rapidly. The recognition of these needs
gave rise to the BETRNet initiative, specifically designed to facilitate
translational “team science” approach to BE-EA research by establishing
a dedicated network of investigators with strong NCI support and effort
coordination.

Patient Registry with
Virtual Biorepository. Central to this collaborative network is the development
of a multi-institutional patient registry that will include clinical, longitudinal,
and epidemiological data and data sets associated with the biospecimens that
are collected and available at each participating site. The cohort of patients
will include individuals at all levels of risk for BE and EA, providing
opportunities for understanding the natural history of the disease and
determining risk stratification criteria (molecular, environmental, and
epidemiological). Such a registry/virtual biorepository is envisioned to
function as a centrally coordinated shared resource. The establishment of this
resource should significantly increase opportunities to develop and assess
novel minimally invasive and noninvasive technologies for patient
stratification and, thereby, improve patient management. Moreover, the resource
is expected to greatly facilitate novel interventions to target premalignant
processes leading to EA. Both aspects should contribute to improving EA
clinical outcomes.

Specific Research Objectives and Requirements
for the BETRNet Coordinating Center

General Requirements for the BETRNet
Coordinating Center:

BETRNet Coordinating Center (to be funded as a result of this FOA) will
have an important role in integrating the efforts of individual BETRNet
Research Centers to be funded under a companion FOA (RFA-CA-10-014). BETRNet Coordinating Center will be expected to
provide administrative and logistic support infrastructure for the BETRNet
Research Centers. The Coordinating Center must be able to connect available
resources and serve as research data management center.

The Coordinating Center will be expected to
integrate activities of all of the awarded BETRNet Research Centers to minimize
resources/effort duplication and utilize existing resources. In addition, the Coordinating Center will have substantial responsibility for ensuring the continued
self-evaluation of BETRNet awardees and the evaluation of the entire BETRNet
Program.

To fulfill these roles, the Coordinating
Center applicant team must have prior experience in coordinating large
multi-site programs, providing infrastructure
to support the required administrative activities of such a program, including,
but not limited to, monitoring and coordinating the joint activities of all the
participating sites, preparing required reports, addressing logistics and
preparing for group meetings, site visits, outcome dissemination, and Steering
Committee meetings.

The Coordinating Center applicants must have
appropriate professional expertise and experience in the areas defined above.
The applicant institution must have the necessary facilities to meet the specific
requirements defined in the FOA.

Strategic Goals for the BETRNet Coordinating
Center:

BETRNet Coordinating Center applicant team must address the following
strategic objectives:

Facilitate
multi-institutional, transdisciplinary translational research through scientific,
administrative, and organizational support with emphasis on efficient
communication, coordination of efforts, and scientific collaboration
across multiple research institutions;

Facilitate and
mediate contacts between BETRNet awardees and NCI program staff members to
allow for efficient interactions, consultations, and oversight functions;

Create and manage a
patient registry with virtual biorepository that will encompass clinical
and demographic information of all patients participating in the BETRNet
program as well as available biospecimens at participating sites;

Create and manage
relevant logistic infrastructure including bioinformatics for research
data management, clinical data monitoring, and other requirements to
support the BETRNet Research Centers; and

Create
opportunities to disseminate results across multiple venues.

Required Structure and Main Components of the
BETRNet Coordinating Center

All BETRNet applicants must address the main
aspects for the proposed Coordinating Center (for details see Section IV.
Content and Form of Application Submission) presented below.

1. Leadership and Administrative Core. The Coordinating Center must be able to provide close
coordination of transdisciplinary research efforts of the BETRNet Research
Centers. This role will require strong leadership, scientific insight, and managerial
capacity to bring diverse teams together.

Because of the central requirement for
interactions across BETRNet Research Centers, the Coordinating Center will be responsible for the following activities:

a) Providing administrative leadership in coordinating
BETRNet activities and serving as a hub for the BETRNet Research Centers and the entire BETRNet Program;

b) Assisting the BETRNet Steering Committee in assembling appropriate
panels such as a subcommittee of experts to advise the Steering Committee;

c) Facilitate the establishment of topical “Working
Groups” across BETRNet awardees as recommended by the Steering Committee (e.g.,
clinical interventions group, a specimen collection and biomarkers group)
relevant to the funded BETRNet research and scientific needs across the Network;

e) Facilitating and mediating contacts between BETRNet
Research Centers awardees and NCI staff members to allow for efficient
interactions, consultations, and oversight functions;

f) Providing logistical and administrative support for all
of the activities of the Steering Committee and its subcommittee(s)/Working
Groups; and

g) Organizing the midterm workshop of BETRNet investigators
(in cooperation with the NCI representatives), monthly
committee calls for all BETRNet Research Centers, and
meetings of Working Groups to
be recommended by the Steering Committee.

The main goals of this core are to facilitate
standardization of metrics, data sharing, and results dissemination across BETRNet
and between BETRNet and the NCI.

The Bioinformatics Core must provide
infrastructure for data collection and archiving to meet standards for common
data systems and future data repositories. Specifically, informatics and data
sharing approaches proposed for the BETRNet Coordinating Center must aim at
achieving compatibility (minimum silver level) with the NCI's caBIG. Applicants are expected to plan using established caBIG
applications, as feasible. In addition, the Core must have capabilities to provide statistical support for study
design across the BETRNet.

3. Patient Registry with Virtual Biorepository Core.BETRNet Coordinating Center applicants
must plan for creating and maintaining a patient registry
with virtual biorepository Core. This Core must set
up a registry database with clinical and demographic information of all
patients participating in the clinical studies under the BETRNet program. In addition, the Core must
collect and include in the registry database information on the availability of
biological specimens at all the BETRNet participating sites. The biospecimen
data must include information about the regulatory approvals of specimen
collections and the level of informed consent.

The Core must allow for efficient sharing of information across the BETRNet
as well as facilitate and track the distribution of available biospecimens to
BETRNet investigators, consistent with achieving the goals of the program.

4. Integration and Self-Evaluation Core. The proposed BETRNet Coordinating Center must have a
well developed capacity to enable timely self-evaluation mechanisms promoting
effective self-correcting actions. In this area, the Coordinating Center will have to closely collaborate with the BETRNet Steering Committee (see below),
individual BETRNet Research Centers, and NCI Program staff members.

This self-evaluation Core should track the
relevant performance benchmarks of each BETRNet Research Center and compare its
performance to the other Centers. Outcomes to be assessed will include peer-reviewed
publications, translational advances, and other factors related to the
effectiveness of a collaborative research model. The outcomes will help the Steering
Committee and individual BETRNet Research Centers to take corrective steps and
optimize their performance.

In addition, to the self-evaluation, the
entire BETRNet program will be subject to external evaluation to be coordinated
by the NCI Program Staff (see below). The self-evaluation of the BETRNet
awardees (and the activities of this Core) will be essential for facilitating
and enhancing the external program evaluation. BETRNet Coordinating Center (and specifically this Integration and Self-Evaluation Core) will be expected to
cooperate with NCI in the evaluation process.

Governance of the BETRNet

The BETRNet (i.e., the Research Centers and Coordinating Center) will be governed by the BETRNet Steering Committee.

Details on the composition and functions of BETRNet
Steering Committee are provided in Section VI.2.A.3, Terms and Conditions of Cooperative
Agreement “Collaborative Responsibilities.”

External Evaluation of the Program

As the efficiency of the funded research is
an increasing priority for NCI, BETRNet awardees will be expected to
participate in an external evaluation process coordinated by involved NCI
program staff members. The purpose of the evaluation process is to monitor and
assess the performance of the BETRNet program toward achieving its goals. This
component includes evaluating the quality and innovation of the research conducted
at the BETRNet Research Centers and Coordinating Center, as well as assessing
critical intermediate determinants of the overall success, such as
infrastructure development and capacity building, linkages, resource and data
sharing arrangements within and among BETRNet components, and the translational
nature of the research.

In terms of the overall impact of the BETRNet
Program, particular focus areas will be improved understanding of EA
carcinogenesis, and the development of EA risk stratification criteria and
patient management modalities that are based on the biological mechanisms of
the disease.

The relevant outcomes to use as measures of
program success will be identified from the conceptual framework presented
earlier and from other theoretical models and empirical evidence in the
literature.

Other Related Funding Opportunities

This FOA is parallel to a separate U01 FOA (RFA-CA-10-015), which solicits applications for the BETRNet Coordinating Center.

This funding opportunity
will use a cooperative agreement award mechanism. In
the cooperative agreement mechanism, the Project Director/Principal
Investigator (PD/PI) retains the primary responsibility and dominant role for
planning, directing, and executing the proposed project, with NIH staff being
substantially involved as a partner with the Principal Investigator, as
described under the Section VI. 2. Administrative
Requirements, "Cooperative Agreement Terms and Conditions of
Award".

2. Funds
Available

The
estimated amount of funds available for support ofone centerawarded as a result of this
announcement is $500,000 for fiscal year 2011. Future year amounts will depend on annual appropriations.

Because the nature
and scope of the proposed research will vary from application to application,
it is anticipated that the size and duration of each award will also vary.
Although the financial plans of the NCI provide support for this program,
awards pursuant to this funding opportunity are contingent upon the
availability of funds and the receipt of a sufficient number of meritorious
applications.

NIH
grants policies as described in the NIH Grants Policy
Statement will apply to the applications submitted and awards made in
response to this FOA.

Any
individualwith the skills, knowledge, and resources necessary to
carry out the proposed research as the PD/PI is invited to work with his/her
institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH support.

NOTE: Investigators
designated as PDs/PIs on any BETRNet Research Center (U54) application cannot
serve as PDs/PIs on a Coordinating Center U01 application.

More
than one PD/PI, or multiple PDs/PIs, may be designated on the application for
projects that require a “team science” approach and therefore
clearly do not fit the single-PD/PI model. Additional
information on the implementation plans, policies and procedures to formally
allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi.All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://grants.nih.gov/grants/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to
apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility
of the investigators and applicant organizations, and should be determined by
the scientific goals of the project. Applications for grants with multiple PDs/PIs
will require additional information, as outlined in the instructions below.
When considering multiple PDs/PIs, please be aware that the structure and
governance of the PD/PI leadership team as well as the knowledge, skills and
experience of the individual PDs/PIs will be factored into the assessment of
the overall scientific merit of the application. Multiple PDs/PIs on a project
share the authority and responsibility for leading and directing the project,
intellectually and logistically. Each PD/PI is responsible and accountable to
the grantee organization, or, as appropriate, to a collaborating organization,
for the proper conduct of the project or program, including the submission of
required reports. For further information on multiple PDs/PIs, please seehttp://grants.nih.gov/grants/multi_pi.

Applications
must have a D&B Data Universal Numbering System (DUNS) number as the
universal identifier when applying for Federal grants or cooperative
agreements. The D&B number can be obtained by calling (866) 705-5711 or
through the web site at http://www.dnb.com/us/.
The D&B number should be entered on line 11 of the face page of the PHS 398
form.

The title and
number of this funding opportunity must be typed in item (box) 2 only of the
face page of the application form and the YES box must be checked.

Applications
with Multiple PDs/PIs

When multiple PD/PIs are
proposed, use the Face Page-Continued page to provide items 3a – 3h for
all PD/PIs. NIH requires one PD/PI be designated as the “contact
PD/PI” for all communications between the PD/PIs and the agency. The
contact PD/PI must meet all eligibility requirements for PD/PI status in the
same way as other PD/PIs, but has no special roles or responsibilities within
the project team beyond those mentioned above. The contact PD/PI may be changed
during the project period. The contact PD/PI should be listed in block 3 of
Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page
1-Continued. When inserting the name of the PD/PI in the header of each
application page, use the name of the “Contact PD/PI, et al.” The
contact PD/PI must be from the applicant organization if PD/PIs are from more
than one institution.

All individuals designated
as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI
role in that system (other roles such as SO or IAR will not give the PD/PI the
appropriate access to the application records). Each PD/PI must include their
respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing
Multiple PDs/PIs will be required to include a new section describing the
leadership plan approach for the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the
section of the Research Plan entitled, “Multiple PD/PI Leadership Plan”,
must be included. A rationale for choosing a multiple PD/PI approach should be
described. The governance and organizational structure of the leadership team
and the research project should be described, and should include communication
plans, process for making decisions on scientific direction, and procedures for
resolving conflicts. The roles and administrative, technical, and scientific
responsibilities for the project or program should be delineated for the
PDs/PIs and other collaborators.

If
budget allocation is planned, the distribution of resources to specific
components of the project or the individual PDs/PIs should be delineated in the
Leadership Plan. In the event of an award, the requested allocations may be
reflected in a footnote on the Notice of Award (NOA).

Prospective
applicants are asked to submit a letter of intent that includes the following
information:

Descriptive title of proposed research;

Name, address, and telephone number of
the Principal Investigator(s);

Names of other key personnel;

Participating institutions; and

Number and title of this funding
opportunity.

Although a letter of
intent is not required, is not binding, and does not enter into the review of a
subsequent application, the information that it contains allows IC staff to
estimate the potential review workload and plan the review.

Applications
must be prepared using the forms found in the PHS 398 instructions for
preparing a research grant application. Submit a signed, typewritten original
of the application, including the checklist, and three signed photocopies in one package to:

Applications
must be received
on or before the application receipt date described above (Section IV.3.A.). If an application is received after
that date, the application may be delayed in the review process or not
reviewed. Upon receipt, applications will be evaluated for completeness by the
CSR and for responsiveness by the reviewing Institute. Incomplete and/or
non-responsive applications will not be reviewed.

The NIH will not
accept any application in response to this funding opportunity that is
essentially the same as one currently pending initial review, unless the
applicant withdraws the pending application. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to a funding opportunity, it is to
be prepared as a NEW application. That is, the application for the funding
opportunity must not include an Introduction describing the changes and
improvements made, and the text must not be marked to indicate the changes from
the previous unfunded version of the application.

All NIH awards
are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants Policy Statement. The Grants Policy
Statement can be found at NIH Grants
Policy Statement.

Pre-award costs
are allowable. A grantee may, at its own risk and without NIH prior approval,
incur obligations and expenditures to cover costs up to 90 days before the
beginning date of the initial budget period of a new award if such costs: 1)
are necessary to conduct the project; and 2) would be allowable under the
grant, if awarded, without NIH prior approval. If specific expenditures would
otherwise require prior approval, the grantee must obtain NIH approval before
incurring the cost. NIH prior approval is required for any costs to be incurred
more than 90 days before the beginning date of the initial budget period of a
new award.

The incurrence
of pre-award costs in anticipation of a competing or non-competing award imposes
no obligation on NIH either to make the award or to increase the amount of the
approved budget if an award is made for less than the amount anticipated and is
inadequate to cover the pre-award costs incurred. NIH expects the grantee to be
fully aware that pre-award costs result in borrowing against future support and
that such borrowing must not impair the grantee's ability to accomplish the
project objectives in the approved time frame or in any way adversely affect
the conduct of the project (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm).

6. Other Submission Requirements

All
application instructions outlined in the PHS398 Application Instructions are to
be followed, with the following additional requirements:

Specific
Aims is limited to 1 page.

Research
Strategy, including tables, graphs, figures, diagrams, and charts is limited
to: 12 pages for Research Center Overview;
12 pages for Leadership
and Administrative Core); 6 pages for Data and Bioinformatics Core; 6 pages for Patient Registry with Virtual Biorepository Core; and 6 pages for Integration and Self-Evaluation Core. See Table of Page
Limits.

BETRNet Coordinating Center (U01) applicants
must demonstrate in the application their ability to meet:

Follow the current PHS 398 instructions to
provide a detailed budget (direct costs) for the entire application for the
first 12-month period (Form page 4) and the entire proposed project period
(Form page 5). Include appropriate budget pages for any sub-contractual
arrangements proposed.

Use additional Form Pages 4 and 5 to provide
detailed separate budget information (first year and cumulative budgets for the
entire project period) for the following individual application components:

Budget pages for
Administrative Core;

Budget pages for
Data and Bioinformatics Core;

Budget pages for
Patient Registry with Virtual Biorepository Core; and

Budget pages for
Integration and Self-evaluation Core.

PHS398 Research Plan Sections

All
application instructions outlined in the PHS398 Application Instructions are to
be followed, with the following additional requirements:

Section 3. Research Strategy of the PHS 398 Research Plan must consist of the following
sub-sections A-E (corresponding to individual application components, see
details below); and

The PHS 398 standard page limit for Research
Strategy is replaced by individual limits indicated below for the new
subsections A-E.

Other sections of the PHS398 Research Plan
remain unmodified and should be completed following standard instructions.

A. Overview of the Proposed Coordinating Center (up to 12 pages)

In this section, describe the following
aspects:

The overall vision for
the BETRNet Coordinating Center;

Major strengths and
critical experience of the research team; and

Innovative value and
potential of the proposed Coordinating Center to function in coordinating
transdisciplinary research on EA conducted through the BETRNet.

B. Leadership and Administrative Core (up to
12 pages)

In this section, describe the following
aspects:

The organization of
the leadership structure;

Available infrastructure
to support the required administrative activities of the BETRNet
including, but not limited to, monitoring and coordinating the activities
of all the BETRNet Research Centers (including participating clinical
sites), preparing required reports, addressing logistics, and preparing
for various BETRNet meetings, site visits, outcome dissemination, Steering
Committee meetings, and periodic meetings and teleconferences; and

Plans for participation
of the Coordinating Center Investigators in the activities of the Steering
Committee including any subcommittee(s).

C. Data and Bioinformatics Core (up to 6
pages)

In this section, describe the following
aspects:

Capabilities to
support proposed projects and data sharing among all BETRNet participating
sites;

Plans to achieve
compatibility of the BETRNet data and informatics with the NCI's cancer
Biomedical Informatics Grid (caBIG);

Plans to use caBIG
applications to facilitate data and resource sharing across BETRNet, as
appropriate; and

Capabilities to
provide statistical support in study design across the BETRNet, if needed.

D. Patient Registry with Virtual Biorepository
Core (up to 6 pages)

In this section, describe the following:

Plans to create a patient
registry with virtual biorepository that will collect and provide clinical
and demographic information of all patients participating in the BETRNet
program;

Plans to collect in
the registry database information about the availability of biological
specimens at all the BETRNet participating sites, including information
about the regulatory approvals of specimen collections and the level of
informed consent and

Mechanisms to
facilitate the sharing and distribution of information and biospecimens across
the BETRNet.

E. Integration and Self-Evaluation Core (up to
6 pages)

In this section, describe the following:

The capacity to
collaborate with the BETRNet Centers and NCI Program Staff;

The capacity to
establish an evaluation system;

Possible categories
to be considered for the performance of each BETRNet Research Center; and

Possible model(s)
for evaluation of the overall initiative.

OTHER REQUIREMENTS

Overall Responsibilities. Applicants must agree to adhere to all the
responsibilities and obligations defined in Section VI.2.A, “Cooperative
Agreement Terms and Conditions of Award.”

Site Visits. Because of the complexity of the BETRNet, NCI program
staff members will conduct at least one administrative site visit. BETRNet
applicants must agree to participate in this process and should plan for one
visit (with appropriate budget, including travel for collaborators and other
necessary costs).

Travel Funds. Applicants must plan appropriate travel funds for the PD(s)/PI(s)
and team leaders to participate in the scientific workshop that will be
conducted in the midterm of the award.

Do
not use the Appendix to circumvent the page limitations. An application that
does not observe the required page limitations may be delayed in the review process.

Resource Sharing
Plan(s)

NIH considers the sharing of unique research
resources developed through NIH-sponsored research an important means to
enhance the value of, and advance research. When resources have been developed
with NIH funds and the associated research findings published or provided to
NIH, it is important that they be made readily available for research purposes
to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing,
this should be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(b) Sharing Model Organisms:
Regardless of the amount requested, all applications where the development of
model organisms is anticipated are expectedto include a
description of a specific plan for sharing and distributing unique model
organisms and related resources, or state appropriate reasons why such sharing
is restricted or not possible. See Sharing
Model Organisms Policy and NIH
Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless
of the amount requested, applicants seeking funding for a genome-wide
association study are expected to provide a plan for submission of GWAS data to the NIH-designatedGWAS data repository, or provide an appropriate
explanation why submission to the repository is not possible. A genome-wide
association study is defined as any study of genetic variation across the
entire genome that is designed to identify genetic associations with observable
traits (such as blood pressure or weight) or the presence or absence of a
disease or condition. For further information, see the Policy for Sharing of
Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088 and http://grants.nih.gov/grants/gwas/.

In addition to the general NIH requirements, the following
provisions specific to this FOA apply:

(d) Specimens Sharing: All BETRNet awardees will be
expected to provide information about the availability of biospecimens at their
institutions as well as associated clinical/demographic information to the
Patient Registry with Virtual Biorepository created and maintained by the Coordinating Center. All BETRNet investigators are expected to be willing to share
biospecimens and related information with other BETRNet investigators pursuant
to the terms of the informed consent and consistent with achieving the goals of
this program. In line with these requirements, BETRNet awardees are expected to structure the informed consent document and other
human subjects procedures with considerations for the wider sharing of data and
specimens collected under the BETRNet award.

Section
V. Application Review Information

1. Criteria

Only the review
criteria described below will be considered in the review process.

2. Review and Selection Process

Review Process

Applications
that are complete and responsive to the FOA will be evaluated for scientific and
technical merit by an appropriate peer review group convened bythe National Cancer Instituteand in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/),
using the review criteria stated below.

As part of the scientific peer
review, all applications will:

Undergo
a selection process in which only those applications deemed to have the
highest scientific and technical merit, generally the top half of
applications under review, will be discussed and assigned an overall
impact/priority score;

Receive
a written critique; and

Receive
a second level of review by National Cancer Advisory Board.

The mission of the NIH is to support science
in pursuit of knowledge about the biology and behavior of living systems and to
apply that knowledge to extend healthy life and reduce the burdens of illness
and disability. As part of this mission, applications submitted to the NIH for
grants or cooperative agreements to support biomedical and behavioral research
are evaluated for scientific and technical merit through the NIH peer review
system.

Overall
Impact

Reviewers will provide an overall impact/priority score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following five scored review criteria, and additional review criteria (as
applicable for the project proposed).

Scored
Review Criteria

Reviewers will consider each of the five review criteria below in
the determination of scientific and technical merit, and give a separate score
for each. An application does not need to be strong in all categories to be
judged likely to have major scientific impact. For example, a project that by
its nature is not innovative may be essential to advance a field.

Significance. Does the project address an
important problem or a critical barrier to progress in the field? If the aims
of the project are achieved, how will scientific knowledge, technical
capability, and/or clinical practice be improved? How will successful
completion of the aims change the concepts, methods, technologies, treatments,
services, or preventative interventions that drive this field?

Investigator(s). Are the PD(s)/PI(s),
collaborators, and other researchers well suited to the project? If Early Stage
Investigators or New Investigators, or in the early stages of independent careers, do they
have appropriate experience and training? If established, have they
demonstrated an ongoing record of accomplishments that have advanced their
field(s)? If the project is collaborative or multi-PD/PI, do the investigators
have complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation. Does the application challenge
and seek to shift current research or clinical practice paradigms by utilizing
novel theoretical concepts, approaches or methodologies, instrumentation, or
interventions? Are the concepts, approaches or methodologies, instrumentation, or
interventions novel to one field of research or novel in a broad sense? Is a
refinement, improvement, or new application of theoretical concepts, approaches
or methodologies, instrumentation, or interventions proposed?

Approach. Are the overall strategy, methodology, and
analyses well-reasoned and appropriate to accomplish the specific aims of the
project? Are potential problems, alternative strategies, and benchmarks for
success presented? If the project is in the early stages of development, will
the strategy establish feasibility and will particularly risky aspects be
managed? If the project involves clinical research, are the plans for: 1)
protection of human subjects from research risks; and 2) inclusion of
minorities and members of both sexes/genders, as well as the inclusion of
children, justified in terms of the scientific goals and research strategy
proposed?

Environment. Will the scientific environment
in which the work will be done contribute to the probability of success? Are
the institutional support, equipment and other physical resources available to
the investigators adequate for the project proposed? Will the project benefit
from unique features of the scientific environment, subject populations, and/or
collaborative arrangements?

In addition to the above review criteria, the
following criteria will be applied to applications in the determination of
scientific merit and the impact/priority score.

A. Overall Vision of the Coordinating Center:

How well will the proposed Coordinating Center serve the goals of BETRNet? How nearly adequate are research
infrastructure, programs, and collaborations to support the BETRNet research
centers?

B. Research Team, Leadership, and
Administrative Core:

Is there adequate evidence for the managerial
and collaborative capabilities of the proposed Coordinating Center leadership? How appropriate is the leadership structure of the proposed Coordinating Center in terms of (a) the overall goals of BETRNet initiative; (b); the
coordination of multiple institutions participating in a given BETRNet Research Center; and (c) the participation in and coordination of cross-BETRNet
activities? Are the backgrounds, expertise, and commitments of the PD(s)/PI(s)
and other key personnel sufficient for the proposed scope of activities and in
line with the overall goals of the BETRNet initiative?

C. Data and Bioinformatics Core:

How well does the proposed core meet the overall
BETRNet goals? Does the core have the appropriate capabilities to support
proposed projects and data sharing among all BETRNet participating sites? How
adequate are the plans to achieve compatibility with the NCI's caBIG as well as the use of caBIG applications to facilitate data and resource
sharing across BETRNet? Does the core have sufficient capabilities to provide
statistical and other support in study design across the BETRNet?

D. Patient Registry with Virtual Biorepository
Core:

How appropriate and balanced are the proposed
plan to create a virtual registry with biorepository? Are the plans well
justified and include appropriate safeguards for privacy and confidentiality
protections of identifiable data? Does the plan describe a program that will efficiently
support the sharing of specimens and information across the BETRNet?

E. Integration and Evaluation Core:

How well does the evaluation plan demonstrate
the capacity of the BETRNet Coordinating Center to collaborate with the BETRNet Research Centers and NCI program staff on critical evaluation of scientific progress,
peer-reviewed publications, web sites, evidence-based dissemination, or new collaborations and partnerships?

Additional Review Criteria

As applicable for the project proposed,
reviewers will consider the following additional items in the determination
of scientific and technical merit, but will not give separate scores for these
items.

Protections for Human Subjects. For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects; 2) adequacy of protection against risks; 3) potential benefits to the
subjects and others; 4) importance of the knowledge to be gained; and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria
for one or more of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate: 1) the justification for the exemption; 2)
human subjects involvement and characteristics; and 3) sources of materials.

Inclusion of Women, Minorities, and Children. When the
proposed project involves clinical research, the committee will evaluate the
proposed plans for inclusion of minorities and members of both genders, as well
as the inclusion of children.

Vertebrate Animals. The committee will evaluate the
involvement of live vertebrate animals as part of the scientific assessment
according to the following five points: 1) proposed use of the animals, and
species, strains, ages, sex, and numbers to be used; 2) justifications for the
use of animals and for the appropriateness of the species and numbers proposed;
3) adequacy of veterinary care; 4) procedures for limiting discomfort,
distress, pain and injury to that which is unavoidable in the conduct of
scientifically sound research including the use of analgesic, anesthetic, and
tranquilizing drugs and/or comfortable restraining devices; and 5) methods of
euthanasia and reason for selection if not consistent with the AVMA Guidelines
on Euthanasia.

Biohazards. Reviewers will assess whether
materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Resubmission Applications. Resubmissions are not allowed for this FOA.

Renewal Applications. Renewals are not allowed for this FOA.

Revision Applications. Revisions are not allowed for this FOA.

Additional Review Considerations

As applicable for the project proposed, reviewers will address
each of the following items, but will not give scores for these items and should
not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations. Foreign are not allowed for this FOA.

Select Agents Research. Reviewers will assess the
information provided in this section of the application, including: 1) the
Select Agent(s) to be used in the proposed research; 2) the registration status
of all entities where Select Agent(s) will be used; 3) the procedures that will
be used to monitor possession use and transfer of Select Agent(s); and 4) plans
for appropriate biosafety, biocontainment, and security of the Select Agent(s).

A
formal notification in the form of a Notice of Award (NoA) will be provided to
the applicant organization. The NoA signed by the grants management officer is
the authorizing document. Once all administrative and programmatic issues have
been resolved, the NoA will be generated via email notification from the
awarding component to the grantee business official

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See also Section
IV.5. Funding Restrictions.

The following Terms and Conditions will be
incorporated into the award statement and will be provided to the Principal
Investigator as well as to the appropriate institutional official, at the time
of award.

2.A. Cooperative Agreement Terms
and Conditions of Award

The following special
terms of award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS grant administration regulations at 45 CFR Parts
74 and 92 (Part 92 is applicable when State and local Governments are eligible
to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and
funding instrument used for this program will be the cooperative agreement an
"assistance" mechanism (rather than an "acquisition"
mechanism), in which substantial NIH programmatic involvement with the awardees
is anticipated during the performance of the activities. Under the cooperative
agreement, the NIH purpose is to support and stimulate the recipients'
activities by involvement in and otherwise working jointly with the award
recipients in a partnership role; it is not to assume direction, prime
responsibility, or a dominant role in the activities. Consistent with this
concept, the dominant role and prime responsibility resides with the awardees
for the project as a whole, although specific tasks and activities may be
shared among the awardees and the NIH as defined below.

2.
A.1. Principal Investigator Rights and Responsibilities

The PD/PI (or multiple PDs/PIs, if applicable)
will have primary authority and responsibility to define objectives and
approaches, and to plan, conduct, analyze, and publish results,
interpretations, and conclusions of studies conducted. The PD/PI assumes
responsibility and accountability to the applicant organization officials and
to the NCI for the performance and proper conduct of BETRNet Coordinating Center research in accordance with terms and conditions of the award.

The Principal Investigator(s) will have the
primary responsibility for:

Determining and
coordinating appropriate approaches and procedures for the collection and integrative
analysis of research data generated by individual BETRNet Research
Centers;

Releasing data and information
on available resources according to the approved plans for timely sharing
of research resources and data generated through the award, as agreed upon
by the BETRNet Steering Committee and NCI Program Staff;

Promoting and
coordinating cross-BETRNet scientific collaboration;

Facilitating the
formation of appropriate Working Groups to promote the exchange of
experiences, protocols, and ideas across the BETRNet;

Participating in the
development of the BETRNet Steering Committee and other BETRNet advisory
subcommittee(s);

Coordinating the organization
of the meetings of the Steering Committee and any advisory groups and
subcommittee(s) as needed;

Participating in the
midterm scientific workshop, and monthly committee calls organized by the BETRNet Coordinating Center;

Cooperating in the
program evaluation process as called upon by NCI Project Scientists and
BETRNet Steering Committee;

Accepting and
implementing all scientific, practical, and policy decisions approved by
the BETRNet Steering Committee to the extent consistent with applicable
grant regulations;

Providing
information to the NCI Program Directors and NCI Project Scientists
concerning progress by submitting annual progress reports in a standard
format;

Providing
information to the NCI Program Directors and NCI Project Scientists
concerning the BETRNet Steering Committee and scientific meetings and
their outcomes; and

Preparing for and
hosting administrative site visits by NCI staff.

The BETRNet Coordinating Center will be
subject to periodic self-evaluation and external evaluation of the entire
BETRNet Program (coordinated by the NIH). The BETRNet Coordinating Center
Awardee will be expected to participate in such evaluations.

All BETRNet institutions/organizations will be
expected to share with other BETRNet awardees knowledge, data, research
materials, and any other resources necessary and relevant to the BETRNet
Program.

All BETRNet awardees (Coordinating Center and BETRNet Research Centers) will be responsible for ensuring that Informatics and data
sharing approaches used are compatible with caBIG.

Awardees will retain custody
of and have primary rights to the data and software developed under these
awards, subject to Government rights of access consistent with current HHS,
PHS, and NIH policies.

2.
A.2. NIH Responsibilities

Designated NCI Program
staff members, acting as Project Scientists, will have substantial programmatic
involvement that is above and beyond the normal stewardship role in awards, as
described below.

Main NCI responsibilities to BETRNet awardees
(both Research Centers and Coordinating Center) include:

Two NCI Project
Scientists having substantial programmatic involvement as the lead
Scientific Program Directors will be designated as NCI voting members on
the BETRNet Steering Committee (for details see section 2.A.3. Collaborative
Responsibilities);

Assisting in
avoiding unwarranted duplications of effort across BETRNet network;

Helping coordinate
collaborative research efforts that involve multiple Research Centers;

Monitoring the
operations of the BETRNet Coordinating Center and Research Centers and making recommendations on overall project directions and allocations of project
funds;

Reviewing the
progress of individual Research Centers and specific activities shared
among the Research Centers and Coordinating Center;

Participating in the
development and evaluation of cross-BETRNet Projects;

Co-organizing and participating
in the BETRNet midterm workshop;

Participating as
Collaborators to the BETRNet investigators in some shared activities, if
appropriate;

Assisting the BETRNet
awardees as a liaison in stimulating their broader interactions with other
NCI and NIH programs to disseminate results and outcomes from the BETRNet
program and effectively leverage existing NIH/NCI resources and
infrastructures; and

Evaluating the
adherence of BETRNet awardees to the approved data and resource sharing
plans and intellectual property plans.

The NCI reserves the right to adjust funding,
withhold, suspend, or terminate the support to those BETRNet awardee
institutions that are unable to meet the performance requirements set forth in
these Terms and Conditions of Award, or significantly change the level of
performance.

The NCI Staff members will
coordinate an external evaluation of the BETRNet Program.

The
substantially involved NCI Project Scientists will not attend peer review
meetings of renewal (competing continuation) and/or supplemental applications.
If such participation is deemed essential, these individuals will seek NCI
waiver according to the NCI procedures for management of conflict of interest.

Additionally,
an NCI program director acting as Program Official will be responsible for the
normal scientific and programmatic stewardship of the award and will be named
in the award notice. Some Program Officials may also have substantial
programmatic involvement (as Project Scientists). In that case, the individual
involved will not attend peer review meetings of renewal (competing
continuation) and/or supplemental applications or will seek NCI waiver as
stated above.

2.A.3.
Collaborative Responsibilities

The BETRNet Steering Committee will serve as the main
governing board for the BETRNet initiative.

The committee will consist of the following
voting members:

Two representatives
from each Research Center (the Center PD(s)/PI(s) or a lead PD/PI and a
designated senior investigator) who will collectively have one vote. For
multi PIs applications, each PI can attend the Steering Committee meetings
on a rotational basis;

Two representatives
from the BETRNet Coordinating Center (the Center PD(s)/PI(s) or a lead
PD/PI and a designated senior investigator) who will collectively have one
vote; and

Two NCI Project
Scientists who will collectively have one vote for the NCI.

Additional NIH staff members may participate
in Steering Committee meetings as non-voting members.

The BETRNet Steering Committee will meet one
time per year in a face-to-face meeting. Two co-chairs of the BETRNet Steering
Committee will be selected for every 12 months by the committee to coordinate
its operation. The BETRNet Steering Committee co-chairs will meet with NCI
Project Scientists – members of BETRNet onetime per month by telephone
conference.

Additional non-voting members to serve in an
advisory capacity may be added to the BETRNet Steering Committee as needed by a
decision of the existing voting committee members. These additional non-voting
members may include other NCI and NIH Program Staff members and/or Program
Staff members from other Federal agencies (e.g., Food and Drug Administration).

The BETRNet Steering Committee will have
primary responsibility for:

Overseeing the
overall organization of the BETRNet initiative and reviewing its research
goals;

Reviewing the
Working Groups to promote the exchange of experiences, protocols, and
ideas across the BETRNet;

Establishing
advisory committees and subcommittees, as necessary, to ensure the
progress of the individual BETRCs as well as of the overall BETRNet
initiative;

Reviewing the
potential of shared support infrastructure(s) at individual BETRCs to
serve the needs of other BETRCs or the entire initiative;

Developing (jointly
with Working Groups) the BETRNet-wide requests for Pilot Projects and
cross-BETRNet Projects, and conducting their evaluation and selection;

Ensuring that the
BETRNet Research Projects and the Coordinating Center take advantage of
existing NCI and NIH resources and programs;

Making
recommendation for re-directing or termination of BETRNet pilot projects
that become unpromising or unproductive;

Scheduling a midterm
workshop at which lead BETRNet investigators will present their scientific
progress and future plans; and

Overseeing and
coordinating the activities of BETRNet awardees towards compatibility of
informatics and data sharing with NCI’s caBIG applications.

The BETRNet Steering Committee will establish
the Scientific Advisory Panel (a subcommittee of experts) to serve the
BETRNet Steering Committee and the awardees.

The Scientific Advisory Panel will be comprised
of scientific experts from outside the BETRNet initiative and be charged with
the following activities:

Reviewing on a
once-per-year schedule the overall progress of the BETRNet and making
appropriate recommendations to strengthen activities in certain areas; and

Developing and
recommending to the Steering Committee criteria for evaluation of pilot
project proposals and the performance of the selected pilot projects.

BETRNet Steering Committee is also expected
to form topic-specific Working Groups, which will be a resource of cross-BETRNet
expertise. Representatives from the NCI organizational units as well as other
NIH institutes or other Federal agencies (e.g., FDA) will participate in Working
Groups as appropriate (but will not serve as chairs of these Working Groups).

Members of the BETRNet network (i.e., BETRCs
awardees and Coordinating Center awardee) will be required to accept and
implement policies approved by the BETRNet Steering Committee.

2.A.4. Dispute Resolution Process

Any
disagreements that may arise in scientific or programmatic matters (within the
scope of the award) between award recipients and the NIH may be brought to
Dispute Resolution. A Dispute Resolution Panel composed of three members will
be convened. It will have three members: a designee of the Steering Committee
chosen without NIH staff voting, one NIH designee, and a third designee with
expertise in the relevant area who is chosen by the other two; in the case of
individual disagreement, the first member may be chosen by the individual
awardee. This special dispute resolution procedure does not alter the awardee's
right to appeal an adverse action that is otherwise appealable in accordance
with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part
16.

A
final progress report, invention statement, and Financial Status Report are required
when an award is relinquished when a recipient changes institutions or when an
award is terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding
opportunity and welcome the opportunity to answer questions from potential
applicants. Inquiries may fall into three areas: scientific/research; peer
review; and financial or grants management issues:

1. Scientific/Research Contacts:

We encourage your inquiries concerning this
funding opportunity and welcome the opportunity to answer questions from
potential applicants. Inquiries may fall into three areas: scientific/research,
peer review, and financial or grants management issues:

Human Subjects Protection:Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative
trials (Phase III). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html). Sharing Research Data:Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their
institutions, on issues related to institutional policies and local IRB rules,
as well as local, State and Federal laws and regulations, including the Privacy
Rule.

Policy
for Genome-Wide Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see http://grants.nih.gov/grants/gwas/.

Access
to Research Data through the Freedom of Information Act:The Office of
Management and Budget (OMB) Circular A-110 has been revised to provide access
to research data through the Freedom of Information Act (FOIA) under some
circumstances. Data that are (1) first produced in a project that is supported
in whole or in part with Federal funds and (2) cited publicly and officially by
a Federal agency in support of an action that has the force and effect of law
(i.e., a regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has provided
guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Sharing of
Model Organisms:NIH is committed
to support efforts that encourage sharing of important research resources
including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm).
All investigators submitting an NIH application or contract proposal, beginning
with the October 1, 2004 receipt date, are expected to include in the
application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Inclusion of
Women And Minorities in Clinical Research:It is the policy
of the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a clear
and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research. This policy results from the NIH Revitalization Act of 1993 (Section
492B of Public Law 103-43). All investigators proposing clinical research
should read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of
Children as Participants in Clinical Research:The NIH
maintains a policy that children (i.e., individuals under the age of 21) must
be included in all clinical research, conducted or supported by the NIH, unless
there are scientific and ethical reasons not to include them.

Required
Education on the Protection of Human Subject Participants:NIH policy
requires education on the protection of human subject participants for all
investigators submitting NIH applications for research involving human subjects
and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy Requirement:In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html)
investigators must submit or have submitted for them their final, peer-reviewed
manuscripts that arise from NIH funds and are accepted for publication as of
April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly
available no later than 12 months after publication. As of May 27, 2008,
investigators must include the PubMed Central reference number when citing an
article in NIH applications, proposals, and progress reports that fall under
the policy, and was authored or co-authored by the investigator or arose from
the investigator’s NIH award. For more information, see the Public Access
webpage at http://publicaccess.nih.gov/.

Standards
for Privacy of Individually Identifiable Health Information:The Department of Health and Human Services (DHHS)
issued final modification to the "Standards for Privacy of Individually
Identifiable Health Information", the "Privacy Rule", on August
14, 2002. The Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the protection
of individually identifiable health information, and is administered and enforced
by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within
specified page limitations. For publications listed in the appendix and/or
Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide
any other information necessary for the review because reviewers are
under no obligation to view the Internet sites. Furthermore, we caution
reviewers that their anonymity may be compromised when they directly access an
Internet site.

Healthy People 2010:The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting
priority areas. This FOA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This
program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not
subject to the intergovernmental review requirements of Executive Order 12372.
Awards are made under the authorization of Sections 301 and 405 of the Public
Health Service Act as amended (42 USC 241 and 284) and under Federal
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the
terms and conditions, cost principles, and other considerations described in
the NIH Grants Policy Statement. The NIH
Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

Loan Repayment Programs:NIH encourages applications for educational loan
repayment from qualified health professionals who have made a commitment to
pursue a research career involving clinical, pediatric, contraception,
infertility, and health disparities related areas. The LRP is an important
component of NIH's efforts to recruit and retain the next generation of
researchers by providing the means for developing a research career unfettered
by the burden of student loan debt. Note that an NIH grant is not required for
eligibility and concurrent career award and LRP applications are encouraged.
The periods of career award and LRP award may overlap providing the LRP
recipient with the required commitment of time and effort, as LRP awardees must
commit at least 50% of their time (at least 20 hours per week based on a 40
hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.